The disease is characterised by two types of brain damage:
- Amyloid plaques (or senile plaques) are made up of aggregates of β-amyloid peptides produced by the cleavage of APP (amyloid precursor protein). In a healthy brain, the precursor is broken down into soluble, non-amyloidogenic fragments (peptides). In Alzheimer’s disease, the precursor is cleaved into highly insoluble β-amyloid peptides, which accumulate abnormally in the brain;
- An accumulation of hyper-phosphorylated Tau proteins in neurons leads to the formation of neurofibrillary degeneration and neuronal death. In normal conditions, this protein plays a part in the stability of neuron structure.
Within the lesions are immune cells responsible for inflammation, which appears at an early stage, before the first signs and symptoms of Alzheimer’s disease, and which appears to play a complex role, both harmful in some respects and beneficial in others.
In the classic form of the disease in elderly subjects, the neurofibrillary degeneration associated with cognitive decline first affects the hippocampus, which is involved in memory processes, and then progressively the limbic system, which manages emotions, and the cortex that controls spatial awareness, gesture control, language, anticipation and behavioural planning.
The cascade of events in the brains of Alzheimer’s patients is becoming better understood, but the complexity of the disease’s biological mechanisms still leaves many questions unanswered.
At the Paris Brain Institute
- LIPIDS IN ALZHEIMER’S DISEASE
Marie-Claude Potier and Stéphane Haïk’s team is seeking to understand the mechanisms involved in the spread of Alzheimer’s disease in the brain and to study the role of lipids in the disease in order to identify new therapeutic targets. Their objectives include studying the interactions between cholesterol and the APP peptide to modulate the production of amyloid aggregates and characterising the location of their production.
This team is interested in the mechanisms by which lesions propagate via neuronal connections, in particular the susceptibility of certain neurons and the resilience of others.
- BRAIN CONNECTIONS DISRUPTED IN ALZHEIMER’S DISEASE
Another area of research being conducted by the teams of Olivier Colliot & Stanley Durrleman and Richard Lévy is the study of changes in brain connections and neuronal networks in Alzheimer’s disease. Using cutting-edge imaging and network analysis techniques, they have recently shown that alterations in brain connections are present from the earliest stages of the disease.